SUMMARY ? BIOANALYTICAL PHARMACOLOGY AND DRUG EVALUATION CORE The discovery that drugs targeting key pathways involved in aging processes can extend the lifespan of mice and other animals, has opened new research avenues where these drugs are become tools for research in the biology of aging, in research focused on age-related diseases, such as Alzheimer's disease, and in research focused on the effects of aging on a specific-organ system, such as the heart or vascular system. A drug- based approach offers a number of experimental advantages including flexibility in the timing of the intervention, the ability to combine drugs with other interventions to assess synergistic or antagonistic interactions, and the ability to readily treat any animal including unique transgenic disease models where genetic approaches could be time consuming or even unfeasible. Further, the built-in potential to eventually move a drug into human studies provides a solid basis of the translational relevance of the work. Consequently an expanding number of investigators are interested in either using existing drugs or developing novel drugs for their research. However, this breakthrough has created new challenges for the field, including (1) the need to ensure that drugs are effectively delivered to experimental animals, (2) the identification of inter-species differences in drug absorption and metabolism that limit the ability to generalize data from one animal to another species, (3) the high costs of conducting initial aging trials in sufficiently powered trials with vertebrates, and (4) the difficulties involved in conclusively linking the biologic effects of a drug to pharmacologic actions on a specific target or pathway. To address these challenges we have developed the Bioanalytical Pharmacology and Drug Evaluation Core (Pharmacology Core) to provide a range of innovative services that do not exist in any other Nathan Shock Center to promote the identification, implementation, and study of drugs in aging studies. Specifically, we will provide: (1) bioanalytical assay development and quantification of drugs in animals (C. elegans to marmosets) used to study aging and (2) the C. elegans model of aging for initial, rapid, and cost-effective testing of the effects of drugs on longevity and specific biological pathways in this animal. The overall purpose of the Pharmacology Core is to promote the application of existing and novel drugs to aging and age-related disease studies. The Core will include expertise in: drug selection; the development and implementation of bioanalytical assays; consultation on pharmaceutical, pharmacokinetic, and pharmacodynamic approaches to drug dosing; the use of the rapid and cost effective C. elegans model for initial aging studies involving drugs; the use of C. elegans genetic and transgenic resources to study drug mechanisms; and the analysis and interpretation of experimental results. Together these services seek to accelerate research and provide assistance at multiple points in the process of applying a drug to aging studies from conducting initial survival studies, investigating or confirming the in vivo mechanism, testing the effects in mice or other mammals, or to applying a drug to research focused on age-related diseases.